PURPOSE: We aimed to examine the role of age-dependent intervention thresholds (ITs) applied to the Fracture Risk Assessment (FRAX) tool in therapeutic decision making for osteoporosis in the Malaysian population.

METHODS: Data were collated from 1380 treatment-naïve postmenopausal women aged 40-85 years who underwent bone mineral density (BMD) measurements for clinical reasons. Age-dependent ITs, for both major osteoporotic fracture (MOF) and hip fracture (HF), were calculated considering a woman with a BMI of 25 kg/m2, aged between 40 and 85years, with a prior fragility fracture, sans other clinical risk factors. Those with fracture probabilities equal to or above upper assessment thresholds (UATs) were considered to have high fracture risk. Those below the lower assessment thresholds (LATs) were considered to have low fracture risk.

RESULTS: The ITs of MOF and HF ranged from 0.7 to 18% and 0.2 to 8%, between 40 and 85years. The LATs of MOF ranged from 0.3 to 11%, while those of HF ranged from 0.1 to 5.2%. The UATs of MOF and HF were 0.8 to 21.6% and 0.2 to 9.6%, respectively. In this study, 24.8% women were in the high-risk category while 30.4% were in the low-risk category. Of the 44.8% (n=618) in the intermediate risk group, after recalculation of fracture risk with BMD input, 38.3% (237/618) were above the ITs while the rest (n=381, 61.7%) were below the ITs. Judged by the Youden Index, 11.5% MOF probability which was associated with a sensitivity of 0.62 and specificity of 0.83 and 4.0% HF probability associated with a sensitivity of 0.63 and a specificity 0.82 were found to be the most appropriate fixed ITs in this analysis.

METHODS: We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.

RESULTS: All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.

METHODS: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws.

FINDINGS: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP).

INTERPRETATION: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.

METHODS: A systematic search of PubMed, EMBASE, and Web of Science was conducted up to June 7, 2024, following PRISMA guidelines to identify studies related to COVID-19 vaccines and POTS. Eligible studies included randomized controlled trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports. Screening, data extraction, and quality assessment were independently performed by two reviewers using the Joanna Briggs Institute Checklists and the Newcastle-Ottawa Scale.

RESULTS: Of the 1,531 articles identified, 10 met the inclusion criteria, encompassing a total of 284,678 participants. These studies included five case reports, two case series, one cross-sectional study, one prospective observational study, and one cohort study. The cohort study reported that the odds of new POTS diagnoses post-vaccination were 1.33 (95% CI: 1.25-1.41) compared to the 90 days prior. In contrast, the post-infection odds were 2.11 (95% CI: 1.70-2.63), and the risk of POTS was 5.35 times higher (95% CI: 5.05-5.68) post-infection compared to post-vaccination. Diagnostic findings across studies included elevated norepinephrine levels and reduced heart rate variability. Reported management strategies involved ivabradine, intravenous therapies, and lifestyle modifications.

METHODS: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure).

RESULTS: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001).

OBJECTIVES: This study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption.

METHODS: A multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance.